Saccharomyces cerevisiae cell wall, extracted

Endpoint summary

Description of key information

Based on the available key study (SIMON, OECD TG 423, GLP, 2020, Klimisch 1), the acute oral LD50 value of the test item Saccharomyces cerevisiae cell wall, extracted was found to be above 2000 mg/kg bw in female rats (no mortality, no clinical signs, no effects on body weights, no macroscopic changes at necropsy). Hence, according to the CLP criteria, the test substance was not classified for acute oral toxicity

Acute inhalation toxicity study was waived because exposure of humans via inhalation is unlikely taking into account the very low vapour pressure of  “Saccharomyces cerevisiae cell wall, extracted” which is estimated to be ≤ 4.60 x 10-2 Pa at 20°C and with a mass median aerodynamic diameter of 60.62 µM with less than 1.2% of particles having a size <= 10 µM.

Acute dermal toxicity study was waived based on the results of the acute oral toxicity study in the rat which demonstrated that Saccharomyces cerevisiae cell wall, extracted is not an acute oral toxic and is not classified as STOT SE (no mortality, no clinical sign, no effects on body weights, no macroscopic changes at necropsy; LD50 > 2000 mg/kg bw).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 July 2020 to 30 November 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch number of test material: AD19K01750
- Expiration date of the lot/batch: 27 July 2021

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Germany GmbH
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 186-200 g
- Fasting period before study: no
- Housing: Group caging (3 animals/cage): Type II. or III. polycarbonate cages - Wood bedding and nest building material
- Diet (e.g. ad libitum): ssniff SM R/M "Autoclavable complete diet for rats and mice (ad libitum)
- Water (e.g. ad libitum): tap water from the municipal supply (ad libitum)
- Acclimation period: at least 5 days
- Method of randomisation in assigning animals to test and control groups : no control group

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 – 24.7°C
- Humidity (%): 37 - 64%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily

IN-LIFE DATES: From: 21 July 2020 To: 06 August 2020

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 100 mg/mL
- Amount of vehicle (if gavage): 20 mL/kg bw
- Justification for choice of vehicle: Preliminar trials allowed to obtain homogenous formulations.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2 groups of 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
* Mortality/ Moribundity: Animals were inspected for signs of morbidity and mortality twice daily (at the beginning and end of each working day).
* Clinical observations: Any clinical sign noted during dosing or at any other occasions was recorded at the time seen.
- Body weights: Recorded on Days -1 (prior to removal of food), 0 (prior to administration), 7 and 14.
- Necropsy of survivors performed: yes
- Clinical signs including body weight: yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred in the study during the 14-day observation period at dose level of 2000 mg/kg bw.

Clinical signs:

other: other: All animals were symptom-free during the 14-day observation period.

Gross pathology:

here was no evidence of the macroscopic changes at dose level of 2000 mg/kg bw at necropsy.

Other findings:

No other findings.

TABLE 1: INDIVIDUAL CLINICAL OBSERVATIONS

 

DOSE LEVEL: 2000 mg/kg bw, Treatment on Day 0

SEX: FEMALE

Cage No.

Animal Number

Observations

Observation days

Frequency

0

1

2

3

4

5

6

7-14

30'

1h

2h

3h

4h

6h

1

5573

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

5574

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

5575

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

2

5576

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

5577

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

5578

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

Standard Footnotes:

+ = present

- = absent

h = hour (s)

' = minute

# = Found dead

M = Moribund

Frequency of observation = number of occurrence of observation / total number of observations

Occurrent severities:

Sl = Slight/Small/Few/Small amount

Mo = Moderate/Several/Moderate amount

Ex = Severe/Large/Many/Large/Extreme amount

 

 

TABLE 2: INDIVIDUAL BODY WEIGHT AND BODY WEIGHT GAIN

 

	Body weights (g)				Absolute weight gain (g)
Days / Period	-1	0	7	14	0-7	7-14	0-14
5573	200	186	212	226	26	14	40
5574	217	198	222	236	24	14	38
5575	212	200	210	211	10	1	11
5576	199	192	219	228	27	9	36
5577	204	195	231	239	36	8	44
5578	207	189	232	245	43	13	56
Mean	206.5	193.3	221.0	230.8	27.7	9.8	37.5
SD	7.0	5.4	9.3	12.0	11.3	5.0	14.8
Max	217	200	232	245	43	14	56
Min	199	186	210	211	10	1	11
N	6	6	6	6	6	6	6

 

 

 

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test item Saccharomyces cerevisiae cell wall, extracted was found to be above 2000 mg/kg bw in female Crl:WI rats. According to the CLP criteria, Saccharomyces cerevisiae cell wall, extracted can be ranked as "No category" for acute oral exposure. According to the GHS criteria, Saccharomyces cerevisiae cell wall, extracted can be ranked as "Unclassified" for acute oral exposure.

Executive summary:

The acute oral toxicity study of Saccharomyces cerevisiae cell wall, extracted in rats was tested according to the acute toxic class method (OECD 423 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.Tris) in Crl:WI Wistar rats. Two groups of three female Crl:WI rats were treated with the test item at dose level of 2000 mg/kg body weight (bw) (Group 1 and Group 2). A single oral treatment was carried out by gavage for each animal. The test item was administered at the dose level of 2000 mg/kgbw, with water as vehicle.

Initially, three females (Group 1) were treated at dose level of 2000 mg/kgbw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in this group; therefore, no further testing was required according to OECD 423 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.tris. Animals were observed during 14psot-treatment for clinical observations, body weight and then necropsied.

The results of the study were:

No mortality occurred in the study during the 14-day observation period at dose level of 2000 mg/kg bw.

All animals were symptom-free during the 14-day observation period.

There were no test item related body weight changes. Body weights were within the range commonly recorded for this strain and age.

There was no evidence of the macroscopic changes at dose level of 2000 mg/kg bwat necropsy.

Conclusion:

Under the conditions of this study, the acute oral LD50value of the test item Saccharomyces cerevisiae cell wall, extracted was found to be above 2000 mg/kg bw in female Crl:WI rats. According to the CLP criteria, Saccharomyces cerevisiae cell wall, extracted can be ranked as "No category" for acute oral exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Reliability 1 study (GLP compliant and guideline study).

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
Exposure of humans via inhalation is unlikely taking into account the very low vapour pressure of “Saccharomyces cerevisiae cell wall, extracted” which is estimated to be ≤ 4.60 x 10-2 Pa at 20°C and with a mass median aerodynamic diameter of 60.62 µM with less than 1.2% of particles having a size <= 10 µM.

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and, in the absence of an in vivo study by the oral route, no systemic effects after dermal exposure are predicted on the basis of non-testing approaches (e.g. read across, QSAR studies)

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
The acute dermal toxicity study was waived based on the results of an acute oral toxicity study.
An OECD 423 TG test (acute toxic class method) was performed with the target substance Saccharomyces cerevisiae cell wall, extracted in femate rats. Initially, three females were treated at dose level of 2000 mg/kgbw. As no mortality was observed, a confirmatory group was treated at the same dose level. No mortality was observed in this group; therefore, no further testing was required. Results from this test showed that no mortality occurred and all animals were symptom-free up to the 14-day observation period. Also, there were no test item related body weight changes and there was no evidence of macroscopic changes at necropsy. Hence, it can be concluded that the acute oral LD50 value of Saccharomyces cerevisiae cell wall, extracted was above 2000 mg/kg bw in female rats and the substance is not classified according to the CLP criteria for acute oral toxicity endpoint.
As Saccharomyces cerevisiae cell wall, extracted does not meet the criteria for classification as an acute toxic or STOT SE by the oral route, an acute dermal toxicity study does not need to be conducted.

Clinical signs:

other: other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

One key study is available for assessment (SIMON, OECD TG 423, GLP, 2020, Klimisch 1):

An OECD 423 TG test (acute toxic class method) was performed with the target substance Saccharomyces cerevisiae cell wall, extracted in femate rats. Initially, three females were treated at dose level of 2000 mg/kgbw. As no mortality was observed, a confirmatory group was treated at the same dose level. No mortality was observed in this group; therefore, no further testing was required. Results from this test showed that no mortality occurred and all animals were symptom-free up to the 14-day observation period. Also, there were no test item related body weight changes and there was no evidence of macroscopic changes at necropsy. Hence, it can be concluded that the acute oral LD50 value of Saccharomyces cerevisiae cell wall, extracted was above 2000 mg/kg bw in female rats and the substance is not classified according to the CLP criteria for acute oral toxicity endpoint.

Justification for classification or non-classification

Based on the available key study, the acute oral LD50 value of the test item Saccharomyces cerevisiae cell wall, extracted was found to be above 2000 mg/kg bw in female Crl:WI rats. Hence, the substance Saccharomyces cerevisiae cell wall, extracted does not require classification for acute oral toxicity according to the CLP criteria.